Design, Synthesis, and Physicochemical Studies of Configurationally Stable β-Carboline Atropisomers.

Axially chiral atropisomers have energetic barriers to rotation, Δ, that prevent racemization of the respective enantiomers. We used computational modeling to develop a suite of 10 bio-inspired 1-aryl-β-carbolines with varying Δ, from which a strong structure-activity relationship was observed for 2-substituted-1-naphthyl substituents. We then synthesized two of these atropisomers, and , by a four-step racemic synthesis and resolved the enantiomers via chiral chromatography.